2. Master Validation Plan A planning tool which outlines all processes that require validation for a medical device project. It identifies, at minimum, the process, scope, methods, and evaluative characteristics to achieve
validation
3. Qualification Log A document which tracks all validation protocols, test method verifications, and master validation plans through numerical listings and descriptions
4. Pre-Validation Checklist A planning tool which documents a team review of related project aspects to assure that validation activities can begin
5. Injection Molding IOQ Protocol Template
A document stating the methods to perform, the data to collect, and the acceptance criteria for conducting installation and operational qualifications
for an injection molding process 6. Injection Molding PQ Protocol Template A document stating the methods to
perform, the data to collect, and the acceptance criteria for conducting a performance qualification for an injection molding process
7. Validation Report Template A document summarizing the results and evidencing whether or not the requirements were met for all executed protocols
8. Protocol Addendum Template A document created as part of the corrective action process, when the validation criteria for an original protocol were not completely satisfied
9. Process Sheet A form used to record injection molding process settings
10. Discrepancy and Deviation Form A form used to document any cases where the approved protocol methods were deviated from or the stated protocol acceptance criteria was not met Table X: Project Deliverables
Validation Procedure
The primary deliverable was the Validation Procedure, which can be found in Appendix X. As stated in Chapter III, the procedure created for the project would establish generalized process validation standards and guidelines for medical classified product, for a team oriented organization. Therefore, the procedure was entitled
“Validation Practice for Medical Product” and consists of eight pages.
The document addresses general procedural aspects, such as roles and responsibilities, see page one of the procedure. It identifies a process owner, the individual who would be responsible for overseeing the procedure. The procedure defines a purpose and scope. It also lists the team members and their responsibilities.
Methods for the validation process begin on page two. Pre-validation activities are explained, along with the use of the “Pre-Validation Checklist”. These activities encourage a team review of the project, with respect to accomplishing validation. It
serves to assure that all supporting items are in place prior to scheduling of an operational qualification. The Qualification Log and the planning tool, Master Validation Plan (MVP), are introduced, followed by an explanation of each validation phase.
Page three of the procedure introduces the concept of a validation protocol, which is defined as a document that describes the validation phase, the testing methods, and the evaluative characteristics that will be utilized to qualify a process. It also lists the protocol content that should be addressed at each validation phase. The protocol templates for injection molding are mentioned, in this section as well. The significance of acceptance criteria and data forms are presented, along with how to obtain protocol approval on page four.
Protocol deviations and discrepancies are explained on page five. Page five also addresses validation scheduling and reporting, including report content and report approvals. Further, the purpose of a validation addendum is provided, along with reference to the protocol addendum template. Page six of the procedure contains definitions for terms that are unique to the validation topic. This page also provides explanation of re-validation. Page seven contains sections for listing related references, documents, records or forms, appendices, revision history, and suggested individuals for training.
Master Validation Plan
The master validation plan (MVP) is a planning tool for the validation process. See Appendix X, for the MVP template developed for use with the procedure. This
document, which should be assigned a control number from the Qualification Log, is designed to consider all equipment and processes requiring validation for a medical
device project. It establishes guidelines for employing statistical tools for analyzing data related to accepting and qualifying molded component(s), assembly equipment and processes. In addition to defining the relationship between quality characteristics, classifications, and acceptable quality levels (AQL), it states the basis for attribute and variable sampling plans.
Besides providing statistical and sampling rationale, the MVP contains a “Validation Matrix”, see pages five and six of the plan, which lists all items to be qualified, such as molds, purchased components, instrumentation, and assembly equipment. It also tracks the qualification task needing performed, such as IQ, OQ, and PQ. For all validation tasks identified, the matrix has a section for documenting the responsible party, for each task.
Beginning with page seven of the MVP, sheets are provided for detailing each qualification in its entirety. The sheets can be customized to account for each item’s unique requirements. For example, a sample sheet is provided for a molded component.
It details each qualification phase, IQ, OQ, and PQ, that must be completed.
Subsequently, it lists the key quality characteristics, along with their acceptance criteria that must be evaluated at each phase. There are also additional qualification outline sheets that are provided for adapting to finishing equipment and purchased components.
Qualification Log
The purpose of the qualification log is to control all validation protocols and reports, test method verifications, and master validation plans, by documenting an assigned number for each. See Appendix X, for the log. The log is comprised of three sheets, a sheet for each qualification type. There is a sheet to track all validations, known as the
“Validation Control Log”. The Validation Control Log contains four columns. One column, labeled “Document #”, documents the number assigned, along with the “VAL”
prefix to designate that it is a validation. In addition, there are columns for identifying the related project, type of qualification (IQ, IOQ, OQ, or PQ), description, and
comments.
There is also a sheet for recording test method verifications, known as “Test Methods Control Log”. This log provides for documenting numbers assigned to test method verification documents, documents which may outline how a measurement instrument will be verified prior to implementation. The number assigned will also contain a prefix,
“TM”, to designate that it is a test method verification. This sheet also contains columns for identifying the related project, description, and comments.
The log also provides a sheet for controlling all master validation plans, identified as
“Master Validation Plan Control Log”. This log provides for documenting numbers assigned to master validation plans. The number assigned will also contain a prefix,
“MVP”, to designate that it is a master validation plan. This sheet also contains columns for identifying the related project, description, and comments.
Pre-Validation Checklist
The pre-validation checklist, see Appendix X, was created for use with the validation procedure. It is a supplemental document used to record that the necessary pre-validation activities were completed. A review of the checklist will indicate that key aspects to achieving validation, such as specifications, training, and procedures, have been reviewed and are in place prior to beginning an operational qualification.
Injection Molding IOQ Protocol Template
The installation and operational qualification requirements for injection molding were addressed by combining both qualifications into one document, entitled an “Installation and Operational Qualification” and abbreviated as IOQ. See appendix X, for the IOQ Protocol Template. A template was created to standardize the protocol documentation and to facilitate protocol development.
The first five pages of the template consist of a cover page, which identifies the protocol number, a table of contents page, an approval page, and a participant
identification log. An introduction section follows, which lists the objective, purpose, and scope of the qualification. It also identifies responsibilities of the qualification team and commonly used abbreviations. Another section, entitled “Data Collection and
Documentation Procedures”, provides instructions for data collection and documentation, while executing the protocol. It also explains the use of attachments, for documenting the qualification data. Furthermore, there are sections that describe the use of the deviation and discrepancy form and an equipment listing.
On page eleven of the template, begins the installation qualification verifications.
The verifications are comprised of a test description, test procedure, acceptance criteria, and test results. The verifications have a corresponding attachment for listing the items checked, related acceptance criteria, actual results, and required sign-offs. A majority of installation verifications are focused on safety and are based on the Plastics Machinery- Horizontal Injection Molding Machines- Safety Requirements for Manufacture, Care, and Use, ANSI/ SPI B151.1-1997.
In addition to safety, the IQ covers environmental and documentation/certification requirements. It assesses any critical instrumentation, auxiliary equipment, and control systems that may comprise the injection system. There are verifications for electrical and supporting utilities. It contains verifications for operator training and cleaning
procedures and schedules. The template also has checks for verifying that a preventative maintenance and spare parts program has been established for the injection system.
The Operational Qualification is represented in the IOQ, by a separate section. The initial verifications in the OQ consist of verifying the operational aspects of the injection press and the mold. The verifications are formatted similar to those for the IQ. They are comprised of a test description, test procedure, acceptance criteria, and test results. They also have a corresponding attachment for listing the items checked, related acceptance criteria, actual results, and required sign-offs. The initial tests confirmed identification of critical instrumentation and training and procedural aspects for the OQ. There were also verifications that assessed that the control, alarm, and security features of the injection press were functioning per the equipment specifications.
The next section of the OQ is entitled “Engineering Studies”, see page 19 of the IOQ template. The engineering studies involve activities required during initial process development. These studies are formatted according to a test description, test procedure, and criteria to proceed. The activities consist of identifying the required settings for the window, viscosity, gate seal, and hold time tests. This development testing is described in the “Process Development” sub-section of the engineering studies. The results are to be recorded on the “Processing Sheet”, see Appendix X.
A key aspect of validation, worse case testing, is addressed by the engineering studies. It is represented by a four corner window study. This study serves to identify the influence of the equipment on the tool, by understanding what effects the process parameters will have on the critical part dimensions and quality characteristics. It will challenge high and low settings with respect to the machine’s process parameters of pressure and temperature.
The window study challenges the ability of the press and mold in producing a capable part at the pressure and temperature combination extremes: high temperature / high pressure, high temperature / low pressure, low temperature / high pressure, and low temperature / low pressure. During these challenges, the molded parts will be taken to their fracture point. A fracture is defined as a condition where the parts begin to exhibit attribute defects. Once the fracture point is identified, the settings for both temperature and pressure will be reduced until an acceptable molded part is obtained. These settings will be considered the worse case parameters capable of producing a part within
specification. The corner settings established during the process development activities and recorded on the processing sheet are used during the window testing.
Once the window study yields the four processing corners and a process centerline, a mold acceptance run can be conducted. The acceptance run serves to confirm the settings established during the process development phases. It consists of a four hour capability study run at the process centerline. During the run, parts will be collected at required intervals and inspected for the defined quality characteristics. All critical part
dimensions must achieve a Cpk ≥ 1.33 per cavity and a Cpk ≥ 1.00 for overall cavity-to-cavity average. All part attributes must meet the required accept/reject criteria per the
specified AQL. The acceptance run activities are described beginning on page 20 of the template. They are formatted according to a test description, test procedure, and
acceptance criteria. The test results are recorded on a corresponding attachment.
The remaining sections of the IOQ template relate to documentation. There is a section that offers concluding remarks and reporting instructions. This section is entitled,
“Conclusion and Protocol Reporting”. The final section, entitled “Reference Documents”, is for listing references, which are the protocol basis.
Injection Molding PQ Protocol Template
A separate protocol template was developed to document the performance qualification (PQ) methods for injection molding. As discussed in Chapter 3, a PQ serves to prove that a process is reproducible and effective. The PQ template describes the methods employed to verify a repeatable molding process.
The template is formatted similar to the IOQ template. The first five pages of the template consist of a cover page, which identifies the protocol number, a table of contents page, an approval page, and a participant identification log. An introduction section follows, which lists the objective, purpose, and scope of the qualification. It also identifies responsibilities of the qualification team and commonly used abbreviations.
Another section, entitled “Data Collection and Documentation Procedures”, provides instructions for data collection and documentation, while executing the protocol. It also explains the use of attachments, for documenting the qualification data. Furthermore, there are sections that describe the use of the deviation and discrepancy form and an equipment listing.
The X section of the template describes the practice of molding three lots of the desired product within the process parameters established during the operational
qualification. The protocol will define a lot size. Part sampling, for the required quality inspections, will be conducted according to the ANSI/ASQC sampling plans, Z1.9-1993 for dimensions and Z1.4-1993 for attributes.
Lot acceptance is based on all critical part dimensions meeting a Cpk ≥ 1.33 per cavity and a Cpk ≥ 1.00 for overall cavity-to-cavity average. In addition, all attributes must meet the defined AQL. If all three lots meet the acceptance criteria, the process will be considered validated. With the acceptance criteria being met, the product produced during the PQ can be saleable.
Validation Report Template
A reporting template was created for use with the validation procedure. See Appendix X, for the report template. For each executed protocol, per the procedure, there must be an accompanying report. The report template can be used for any type of validation protocol, IQ, IOQ, OQ, PQ, or even an addendum. The report summarizes validation results and presents evidence that the protocol requirements were or were not met.
The report template developed is comprised of several sections. It contains an introduction, which includes an objective statement, approval section, and applicable document listing. It includes an executive summary, which provides a summary of the results. It contains a section, labeled as the system description, for documenting the equipment involved in the qualification. A testing results section is included for stating the results of the protocol testing and explaining any deviations or discrepancies that
might have occurred. A conclusion section is provided for stating whether or not the requirements of the protocol have been met. There is also a section, entitled ongoing controls, for assuring that the validated system remains in a state of validation. In addition, an appendix can be created to file all data compiled during protocol execution.
Protocol Addendum Template
The validation procedure permits use of a protocol addendum, as part of a corrective action process. An addendum protocol may be used to supplement the results of an original protocol, when the original protocol requirements were not met. See Appendix X, for the protocol addendum template.
A protocol addendum is similar to the original protocol, except that the introduction should reference the original protocol and explain the discrepancy or incident that the addendum is to address. The addendum may include all or part of the original protocol and must be reported, reviewed, and approved. Each addendum must be assigned a number from the validation control log. The number should be followed by the letters
“PA” to distinguish a protocol addendum. The related report should be distinguished by the letters “RA”.
Process Sheet
A form, entitled “Process Sheet”, was created for use with the validation procedure, for documenting all key injection molding process parameters and information. See
Appendix X, for the form. The process sheet contains a general section for identifying the mold, number of cavities, material, additives, shot weight, and cycle time. Specific to processing, it contains records for plastic temperature, plastic fill rate, plastic pressures after transfer, plastic cooling, and clamping/ejection.
Discrepancy and Deviation Form
Another form, entitled “Discrepancy and Deviation Form”, was created for use with the validation procedure. This form documents any case where the approved protocol methods were deviated from, defined as a “deviation” by the procedure, or where the stated protocol acceptance criteria was not met, defined as a “discrepancy” by the procedure. See Appendix X, for the form. The top portion of the form identifies the related protocol and allows for a selection between a deviation and a discrepancy.
Depending upon which is selected, the form user is directed to the appropriate section for further completion.
The information required to enter a deviation is the assignment of a consecutive number, the protocol section/page that was affected, and a brief description of the change. Spaces are provided for the person making the entry, to date and sign. For a discrepancy entry, a consecutive number must be assigned, the protocol section/page that was affected, and a brief description of the occurrence must be completed. The person entering must sign and date the entry as well. The investigation and root cause section must be completed by an assigned individual, who should sign and date the entries. The corrective action section should be completed by the assigned individual, who should sign and date their entry. A section for documenting that the discrepancy was reviewed and resolved accordingly should be completed, by an individual responsible for the protocol corrective actions.
Gap Analysis Results
For the project, a gap analysis was conducted to prove that the procedure developed achieved compliance to section 820.75, “Process Validation”, of the Quality System
Regulation, 21CFR-Part 820. The procedure’s compliance state was assessed by answering a questionnaire, which was developed from the regulation, 21 CFR-Part 820, Subpart G- Production and Process Controls, Section 820.75 Process Validation.
The questionnaire was designed to identify gaps in methods established for process validation. Appendix X contains the gap analysis that was completed for the project.
Five questions were created for the assessment. All five questions were answered, by the researcher. For each response, supporting evidence was provided. Supporting evidence consisted of referencing the applicable section of the procedure or related documentation. The related documentation could have been forms, templates, plans, or logs that were created specifically for use with the procedure.
The first question assessed whether a method exists for documenting validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated. A “Yes”
The first question assessed whether a method exists for documenting validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated. A “Yes”